The present invention relates to an anion-complexing compound with the formula I of the formula sheet, wherein
R1 is a rest selected from the group of rests with the formulas II, III, and IV of the formula sheet; of which the ring may or may not be substituted with 1 to 3 R2 groups which may or may not be different from each other, wherein R2 represents alkyl or alkoxy;
Yxe2x80x2 represents a xe2x80x94NHC(X)NH-group, and
Yxe2x80x3 represents a rest selected from the group xe2x80x94NHC(Xxe2x80x2)xe2x80x94, xe2x80x94C(Xxe2x80x2)NHxe2x80x94 and xe2x80x94NHC(Xxe2x80x2)NHxe2x80x94, wherein
X and Xxe2x80x2, independently of one another, represent a sulphur or oxygen atom;
A represents an aromatic 6-ring which may or may not be substituted with 1 or 2 R3 groups, which R3 groups, independently of each other, represent alkyl, alkoxy, NO2, or a halide selected from the group consisting of fluorine and chlorine; and
R4, R4xe2x80x2 are either
a) identical, representing aryl that may or may not be substituted with 1 or 2 R3 groups, an alkyl, an acyl and an aryl sulphonyl which may or may not be substituted with 1 or 2 R3 groups;
or
b) together form a single rest, which rest is selected from the group of a rest with the formula V of the formula sheet, which may or may not be substituted with 1 or 2 R3 groups, and an alkyl group with the formula xe2x80x94(CH2)nxe2x80x94 wherein n is 2 to 6.
Alkyl in the present application is to be understood to be a hydrocarbon rest which may or may not be branched, having a chain length of 1 to 15 carbon atoms. The term alkoxy is understood to mean an xe2x80x94OR group, wherein R is an alkyl as previously defined. Aryl is understood to be a group according to formula V of the formula sheet, wherein R is as previously defined. An acyl group is understood to be xe2x80x94C(O)R or an xe2x80x94C(O)Ar, wherein R stands for alkyl and Ar for aryl, both as previously defined.
Nishizawa, S. et al. (ref. 1) describe anion recognition by neutral urea and thiourea compounds with an anion-complexing activity. These compounds differ from the compounds according to the present invention in particular, through the smaller number of hydrogen bonds provided by the (thio)urea groups (2). As R1, which links the (thio)urea group, a rest derived from 1,3-bis(amino methyl) benzene is described.
Buehlmann P. et al. (ref. 2; same authors as ref. 1) have described neutral bis-(thio)urea compounds. The compounds differ from the compounds of the present invention in particular in the smaller number of hydrogen bonds provided by the (thio)urea groups (2). Also described as R1, which binds the (thio)urea groups, is a 2,7-di-tert.-butyl-9,9-dimethyl-4,5-xanthene diamine-derived rest.
Nishizawa, S. et al. (ref. 3) describe the application of compounds disclosed in Ref. 1 for an anion-selective electrode.
Xiao, K. P. et al. (ref. 4, co-authors are among others Nishizawa and Buehlmann) describe the use of the bis-thio-ureaxanthene derivative described in ref. 2 in a membrane for a chloride-ion-selective electrode.
All the above-described prior art compounds relate to bis(thio)urea compounds capable of donating four hydrogen bonds for binding negatively charged ions. The compounds according to the present invention differ from the known compounds in particular in the larger number (6 or more) of hydrogen bonds provided. Despite the fact that negatively charged ions are still bound by maximally four hydrogen bonds from (thio)urea, the compounds according to the present invention have surprisingly been shown to possess a strong affinity for (dihydrogen) phosphate ions.
According to a favourable embodiment, Yxe2x80x3 represents a (thio)urea group, and R4 and R4xe2x80x2 an aryl group.
Surprisingly, a compound according to the present invention in which R4 and R4xe2x80x2 are aryl sulphonyl, but in particular aryl, has been found to bind two (dihydrogen) phosphate groups, with the phosphate groups interacting together by means of a hydrogen bond. Without the intention of being bound to any theory, it is believed that said interaction leads to an increased affinity constant that was observed.
According to a further favourable embodiment at least one of X and Xxe2x80x2 is a sulphur atom.
Such compounds were shown to exhibit higher affinity constants for (dihydrogen)phosphate ions.
According to a further favourable embodiment R1 is substituted with two R2 groups.
It has been found that such compounds are better able to bind anions. Without wishing to be tied to any theory, it is believed that the substituents help to prevent mutual interactions between molecules of the compounds according to the invention, such as hydrogen bonds and xcfx80xe2x80x94xcfx80 stacks, resulting in hydrogen bonds being no longer available for binding anions. Suitable R2 groups are, for example, isopropyl groups.
A method of preparing an anion-complexing compound with formula I of the formula sheet, wherein a compound selected from the group comprising the compounds VI, VII and VIII of the formula sheet and R2 is as previously defined, is reacted with, in respect of the number of NH2 groups, a stoichiometric amount of a compound with the formula IX of the formula sheet, wherein R3 is as previously defined, yielding an intermediate product with the formula X of the formula sheet, with R1 representing the corresponding rest having one of the formulas II, III and IV;
the compound with the formula X is reduced yielding a compound with the formula XI of the formula sheet; and
the compound with the formula XI is reacted with a compound selected from the group comprising R5NCXxe2x80x2, R5COCl, R5SO2Cl, R6(NCXxe2x80x2)2, R6(COCl)2, and R6(SO2Cl)2,
wherein R5 represents an aryl which may or may not be substituted with 1 or 2 R3 groups, an alkyl, an acyl and an arylsulphonyl which may or may not be substituted with 1 or 2 R3 groups; and R6 represents a rest selected from the group of a rest with the formula V of the formula sheet, which may or may not be substituted with 1 or 2 R3 groups, and an alkyl group with the formula xe2x80x94(CH2)nxe2x80x94 in which n is 2 to 6, yielding a compound with the formula I.
With respect to the last step it is observed that the reaction with an R5-comprising compound results in non-macro cyclic compounds, and those with an R6-comprising compound result in macro cyclic compounds with the formula I.
The invention further relates to an ion-selective membrane comprising a compound according to the invention which is incorporated in a polymeric carrier material.
Such a membrane may be utilized for carrying out separations, analyses, and in particular for sensors. A suitable polymeric carrier material is, for instance, PVC. The compound according to the invention may in accordance with coupling techniques that are known in the art, be coupled to the polymeric carrier material. Alternatively, the compound may also be dissolved in the polymeric carrier material. In particular the groups R2 and R3 could be suitably chosen for this purpose and may, for example, be alkyl.
Therefore the invention also relates to a sensor provided with a compound or a membrane according to the invention.
The sensor itself may be any suitable sensor known in the art, such as an ISFET. The compound may be applied, optionally covalently, to the surface of the sensor, using techniques for coupling molecules to a surface which are generally known in the art.
To the person skilled in the art it will be obvious that the compounds defined in the present application may optionally be substituted with one or more groups that essentially do not change the anion-complexing activity, in other words the affinity and/or the selectivity, of the compounds. This may, for example, be the case if the compound has to be coupled to a carrier or has to be made compatible with a matrix in which it is to be incorporated. Such compounds fall within the scope of the invention.